Large vessel ischemic stroke represents the most disabling subtype. While t-PA and endovascular thrombectomy can recanalize the occluded vessel, good clinical outcomes are not uniformly achieved. We ...propose that supplementing endovascular thrombectomy with superselective intra-arterial (IA) verapamil immediately following recanalization could be safe and effective. Verapamil, a calcium channel blocker, has been shown to be an effective IA adjunct in a pre-clinical mouse focal ischemia model. To demonstrate translational efficacy, mechanism, feasibility, and safety, we conducted a group of translational experiments. We performed in vivo IA dose–response evaluation in our animal stroke model with C57/Bl6 mice. We evaluated neuroprotective mechanism through in vitro primary cortical neuron (PCN) cultures. Finally, we performed a Phase I trial, SAVER-I, to evaluate feasibility and safety of administration in the human condition. IA verapamil has a likely plateau or inverted-U dose–response with a defined toxicity level in mice (LD50 16–17.5 mg/kg). Verapamil significantly prevented PCN death and deleterious ischemic effects. Finally, the SAVER-I clinical trial showed no evidence that IA verapamil increased the risk of intracranial hemorrhage or other adverse effect/procedural complication in human subjects. We conclude that superselective IA verapamil administration immediately following thrombectomy is safe and feasible, and has direct, dose–response-related benefits in ischemia.
Platelet function testing prior to flow diversion procedures, although initially heavily debated, has seen a substantial increase in its adoption to assess the risk of operative and perioperative ...thrombotic and hemorrhagic events. This meta-analysis was conducted to assess platelet function testing, particularly the VerifyNow Platelet Reactivity Unit (PRU) assay, for a relationship between the reported assay PRU value and thrombotic and hemorrhagic events.
The currently available literature (2013-2018) was surveyed with PubMed and Google Scholar searches. Included studies were those for which there were at least 30 cases during the study period, for which VerifyNow platelet reactivity unit values were obtained prior to the procedures and for which intraoperative and perioperative adverse events were noted. PRU value cut-offs ranging from >200 to >240 comprised the hyporesponse group while values ranging from <60 to <70 comprised the hyper-response group. The data were subject to statistical analysis to assess the relationship between PRU values and thrombotic and hemorrhagic events. The collected data were subsequently statistically analyzed to assess for publication bias.
The searches yielded 27 studies, of which 12 met the inclusion criteria for the meta-analysis. The meta-analysis included data from 1464 reported Pipeline cases. The study included 273 men and 1177 women with a mean age across the analyzed procedures of 58 years (range 25-85). After loading with antiplatelet medications, preprocedural platelet hyper-responsiveness was associated with a greater incidence of hemorrhagic events with an increased absolute risk of 12%, but showed no relationship with thrombotic events. Preprocedural platelet hyporesponsiveness was associated with a greater incidence of thrombotic events with an absolute risk of 15%, but showed no relationship with hemorrhagic events.
VerifyNow PRU values that correspond to platelet hyporesponse or hyper-response to dual antiplatelet therapy are associated with a higher risk of thrombotic and hemorrhagic events, respectively. Thus, the PRU value may offer some predictive value for these events.
Ischemic stroke remains one of the most debilitating diseases and is the fifth leading cause of death in the US. The ability to predict stroke outcomes within the acute period of stroke would be ...essential for care planning and rehabilitation. The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC; clinicaltrials.gov NCT03153683) study collects arterial blood immediately distal and proximal to the intracranial thrombus at the time of mechanical thrombectomy. These blood samples are an innovative resource in evaluating acute gene expression changes at the time of ischemic stroke. The purpose of this study was to identify inflammatory genes and important immune factors during mechanical thrombectomy for emergent large vessel occlusion (ELVO) and which patient demographics were predictors for stroke outcomes (infarct and/or edema volume) in acute ischemic stroke patients.
The BACTRAC study is a non-probability sampling of male and female subjects (≥18 year old) treated with mechanical thrombectomy for ELVO. We evaluated 28 subjects (66 ± 15.48 years) relative concentrations of mRNA for gene expression in 84 inflammatory molecules in arterial blood distal and proximal to the intracranial thrombus who underwent thrombectomy. We used the machine learning method, Random Forest to predict which inflammatory genes and patient demographics were important features for infarct and edema volumes. To validate the overlapping genes with outcomes, we perform ordinary least squares regression analysis.
Machine learning analyses demonstrated that the genes and subject factors CCR4, IFNA2, IL-9, CXCL3, Age, T2DM, IL-7, CCL4, BMI, IL-5, CCR3, TNFα, and IL-27 predicted infarct volume. The genes and subject factor IFNA2, IL-5, CCL11, IL-17C, CCR4, IL-9, IL-7, CCR3, IL-27, T2DM, and CSF2 predicted edema volume. The overlap of genes CCR4, IFNA2, IL-9, IL-7, IL-5, CCR3, and IL-27 with T2DM predicted both infarct and edema volumes. These genes relate to a microenvironment for chemoattraction and proliferation of autoimmune cells, particularly Th2 cells and neutrophils.
Machine learning algorithms can be employed to develop prognostic predictive biomarkers for stroke outcomes in ischemic stroke patients, particularly in regard to identifying acute gene expression changes that occur during stroke.
Stent-assisted coiling of wide-necked intracranial aneurysms (IAs) using the Neuroform Atlas Stent System (Atlas) has shown promising results.
To present the primary efficacy and safety results of ...the ATLAS Investigational Device Exemption (IDE) trial in a cohort of patients with posterior circulation IAs.
The ATLAS trial is a prospective, multicenter, single-arm, open-label study of unruptured, wide-necked, IAs treated with the Atlas stent and adjunctive coiling. This study reports the results of patients with posterior circulation IAs. The primary efficacy endpoint was complete aneurysm occlusion (Raymond-Roy (RR) class I) on 12-month angiography, in the absence of re-treatment or parent artery stenosis >50%. The primary safety endpoint was any major ipsilateral stroke or neurological death within 12 months. Adjudication of the primary endpoints was performed by an imaging core laboratory and a Clinical Events Committee.
The ATLAS trial enrolled and treated 116 patients at 25 medical centers with unruptured, wide-necked, posterior circulation IAs (mean age 60.2±10.5 years, 81.0% (94/116) female). Stents were placed in all patients with 100% technical success rate. A total of 95/116 (81.9%) patients had complete angiographic follow-up at 12 months, of whom 81 (85.3%) had complete aneurysm occlusion (RR class I). The primary effectiveness outcome was achieved in 76.7% (95% CI 67.0% to 86.5%) of patients. Overall, major ipsilateral stroke and secondary persistent neurological deficit occurred in 4.3% (5/116) and 1.7% (2/116) of patients, respectively.
In the ATLAS IDE posterior circulation cohort, the Neuroform Atlas Stent System with adjunctive coiling demonstrated high rates of technical and safety performance.
https://clinicaltrials.gov/ct2/show/NCT02340585.
A previously healthy 23-month-old girl presented with acute paraparesis and bilaterally upgoing toes. MRI revealed a spinal perimedullary arteriovenous fistula (PMAVF) between T6 and the conus ...medullaris. Trans-arterial Onyx® embolization was performed. She had complete recovery post-therapy. Follow-up MRIs showed no recurrence of PMAVF. PMAVFs, or type IV arteriovenous malformations, are intradural spinal vascular abnormalities (in contrast to dural arteriovenous fistulas) that lack a nidus (as opposed to type II-III arteriovenous malformations). Asymptomatic PMAVFs are uncommon; most cause slowly progressive medullary/radicular signs, although symptoms can develop acutely. When treated, PMAVFs typically have a more favorable prognosis than other spinal arteriovenous malformations.
Abstract only
Introduction
: We sought to determine a distance threshold where mode of transportation impacted treatment options for potential thrombectomy patients.
Methods
: We retrospectively ...reviewed transferred stroke patients to our comprehensive stroke center within 8 hours of onset from January 2017 to December 2019. In our analysis, all patients had a CTA confirmed large vessel occlusion, NIHSS >10 and arrived within 8 hours of onset as a candidate for thrombectomy. Patients were not treated with thrombectomy if they presented with a completed infarct or hemorrhagic conversion. Patients were transferred by air or ground based on availability and safety. Transfers were grouped based on distance: 0–30 miles, 31–60 miles, 61–90 and > 90 miles. We performed a binomial logistic regression for each distance group to determine a threshold where the odds of receiving thrombectomy statistically decoupled based on mode of transportation.
Results
: Of the 243 patients reviewed, 52.1% (126) received thrombectomy. Transport for 50.8% (123) patients was by air. Hospitals transferring within 0–30 miles accounted for 26.6% (65); 31–60 miles accounted for 22.1% (54); 61–90 miles accounted for25.8% (63) and >90 miles accounted for 24.8% (60). The odds of receiving a thrombectomy were significantly higher with air transportation (OR 3.0, CI 1.04‐8.74, p = 0.043) at a distance threshold of >90 miles. At a distance threshold of 10 to 30 miles, the odds of receiving a thrombectomy were significantly higher with ground transportation (OR 5.5, CI 1.15‐26.14, p = 0.032). There was no difference between modes of transportation for 31 to 90 miles.
Conclusions
: Our analysis suggests that air transport beyond 90 miles increases the odds of receiving a thrombectomy for patients arriving within 8 hours of symptom onset. Ground transport, rather than air transport, between 10 and 30 miles may be more beneficial. Our results suggest that specific regional transport thresholds based on distance do exist and if recognized and altered can result in more favorable transfers.
Background and Purpose- The WEAVE trial (Wingspan Stent System Post Market Surveillance) is a postmarket surveillance trial mandated by the Food and Drug Administration to assess the periprocedural ...safety of the Wingspan Stent system in the treatment of symptomatic intracranial atherosclerotic disease. Methods- A total of 152 consecutive patients who met the Food and Drug Administration on-label usage criteria were enrolled at 24 hospitals and underwent angioplasty and stenting with the Wingspan stent. On-label criteria included age 22 to 80 years, symptomatic intracranial atherosclerotic stenosis of 70% to 99%, baseline modified Rankin Scale score ≤3, ≥2 strokes in the vascular territory of the stenotic lesion with at least 1 stroke while on medical therapy, and stenting of the lesion ≥8 days after the last stroke. The primary analysis assessed the periprocedural stroke, bleed, and death rate within 72 hours of the procedure with adjudication by a core study Stroke Neurologist. Results- The trial was stopped early after interim analysis of 152 consecutive patients demonstrated a lower than expected 2.6% (4/152 patients) periprocedural stroke, bleed, and death rate. This was lower than the 4% periprocedural primary event safety benchmark set for the interim analysis in the study. A total of 97.4% (148/152) patients were event-free at 72 hours, 1.3% (2/152) had nonfatal strokes, and 1.3% (2/152) of patients died. Conclusions- With experienced interventionalists, and proper patient selection following the on-label usage guidelines, the use of the Wingspan stent for intracranial atherosclerotic disease demonstrated a low periprocedural complication rate and excellent safety profile. This is the largest on-label, multicenter, prospective trial of the Wingspan stent system to date with the lowest reported complication rate. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02034058.
Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We ...hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation.
STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass.
A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients (
<0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06-1.79;
=0.02). Likewise, excellent outcome (modified Rankin Score 0-1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13-1.92;
=0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer;
=0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier.
In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640.
Mechanical thrombectomy with stent retrievers has become standard of care for treatment of acute ischemic stroke patients because of large vessel occlusion. The STRATIS registry (Systematic ...Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) aimed to assess whether similar process timelines, technical, and functional outcomes could be achieved in a large real world cohort as in the randomized trials.
STRATIS was designed to prospectively enroll patients treated in the United States with a Solitaire Revascularization Device and Mindframe Capture Low Profile Revascularization Device within 8 hours from symptom onset. The STRATIS cohort was compared with the interventional cohort of a previously published SEER patient-level meta-analysis.
A total of 984 patients treated at 55 sites were analyzed. The mean National Institutes of Health Stroke Scale score was 17.3. Intravenous tissue-type plasminogen activator was administered in 64.0%. The median time from onset to arrival in the enrolling hospital, door to puncture, and puncture to reperfusion were 138, 72, and 36 minutes, respectively. The Core lab-adjudicated modified Thrombolysis in Cerebral Infarction ≥2b was achieved in 87.9% of patients. At 90 days, 56.5% achieved a modified Rankin Scale score of 0 to 2, all-cause mortality was 14.4%, and 1.4% suffered a symptomatic intracranial hemorrhage. The median time from emergency medical services scene arrival to puncture was 152 minutes, and each hour delay in this interval was associated with a 5.5% absolute decline in the likelihood of achieving modified Rankin Scale score 0 to 2.
This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02239640.
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